CN107865982A - Medicine-coated balloon - Google Patents
Medicine-coated balloon Download PDFInfo
- Publication number
- CN107865982A CN107865982A CN201610865184.7A CN201610865184A CN107865982A CN 107865982 A CN107865982 A CN 107865982A CN 201610865184 A CN201610865184 A CN 201610865184A CN 107865982 A CN107865982 A CN 107865982A
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- Prior art keywords
- medicine
- acid
- coated balloon
- alcohol
- carrier
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/08—Materials for coatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/80—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special chemical form
- A61L2300/802—Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/06—Coatings containing a mixture of two or more compounds
Abstract
The invention discloses a kind of medicine-coated balloon, including balloon body and the medication coat for being covered in the balloon body surface, the medication coat to contain active medicine and carrier, and the active medicine includes anti-proliferative drug, and the carrier includes transdermal enhancer.It is of the present invention to use the transdermal enhancer that medicine rapid osmotic be promoted to absorb as carrier so that medicine upon discharge, the tissue that rapid osmotic enters at disease sites, improves absorptivity of the medicine in the illing tissue of vascular system or other body lumens.Can solve in Clinical practice, after medicine-coated balloon inserts human body, medicine is slow to penetrating for target lesion position, medicine is not absorbed the shortcomings that just being washed away and being lost in by high speed blood flow also by blood vessel, and due to improving the dose being absorbed by tissue, high amount of drug is able to be retained in tunicae media vasorum, can continue to play drug effect suppression ISR at a specified future date.
Description
Technical field
The present invention relates to interventional medical device, and in particular to medicine-coated balloon.
Background technology
Medicine-coated balloon belongs to insertion type apparatus, and its principle is in common balloon surface supported active medicine, is delivered to
Behind the target lesion position of blood vessel, by the inflation of sacculus, medicine is set fully to be contacted with vascular wall, so as to eliminate target lesion portion
Position it is at a specified future date narrow.
In addition to capillary and capillary lymph duct, vascular wall from tube chamber face out it is general be divided into inner membrance, middle film and
Outer membrane.Inner membrance is the innermost layer of vascular wall, is made up of endothelium and subendothelial layer.Endothelial cell and substrate form the fine and close screen of permeability
Barrier, film during liquid, gas and this selective permeable barrier of macromolecular substances enter.The thickness and constituent of middle film are because of blood
Pipe species and it is different.Main artery has a little smooth muscle based on elastic membrane；Middle artery is mainly made up of smooth muscle.
Therefore, in medicine-coated balloon interventional procedure, the medication coat of balloon surface is after target lesion position is reached, by ball
The elution of capsule surface, discharge to diseased region blood vessel, can not all play drug effect in fact.Wherein only absorbed simultaneously by endangium
The medicine competence exertion curative effect of film layer of smooth muscle cells, the neoplasm for suppressing smooth muscle cell and reduction are narrow again in intravasation
Narrow rate.Because reangiostenosis is a chronic process, by endangium absorb and enter tunicae media vasorum dose it is more, medicine
Also just corresponding more long in target lesion position vascular tissue residence time, the effect for suppressing reangiostenosis is better.And in sacculus
In short some minutes of target lesion contacts blood, when medication coat is discharged to blood vessel from balloon surface, due to
The speed that medicine is absorbed by blood vessel endothelium is very slow, and high amount of drug is not absorbed also just have been washed away by high speed blood flow, can not be ensured
The medicine of sufficient amount passes through the neoplasm that film in inner membrance intravasation suppresses smooth muscle cell, can not more ensure to suppress blood for a long time
Pipe ISR.
Existing medicine-coated balloon can add carrier and additive in medication coat, to increase the dissolubility of medicine,
And improve the drug release rate at once of medicine (i.e.：Reprinting rate).And these carriers and additive are typically only capable to ensure active medicine
Within the short time that sacculus contacts with lesion target vessel, discharge as far as possible to diseased region vascular wall, Wu Fabao rapid, high volume
Card release to the medicine of blood vessel is quickly absorbed by vascular tissue, does not wash away loss by blood；Further, since without enough work
Property medicine pass through inner membrance intravasation in film, can be retained in tunicae media vasorum layer for a long time necessarily without enough drug and persistently play medicine
Effect, suppresses reangiostenosis at a specified future date.
The content of the invention
Based on this, it is necessary to provide a kind of medicine-coated balloon, it can meet in very short interventional procedure, greatly
Amount medicine is quickly transferred to the vascular wall at local target lesion position this premise from balloon surface, it is often more important that, moreover it is possible to accelerate
The speed that medicine is absorbed by blood vessel endothelium, make medicine be not easy to wash away loss by lasting blood flow, and then improve and pass through endangium
The medicine total amount of film in intravasation, ensure, in intervention Post operation, still there is enough drug to be retained in tunicae media vasorum layer for a long time
Drug effect is persistently played, suppresses ISR at a specified future date.
The absorption process of film during anti-restenosis drugs or anti-proliferative drug are entered by inner skin surface, mainly due to interior epidermis
It is poor drug concentration to be present in the drug concentration in face and tunicae media vasorum, medicine by way of Passive diffusion infiltration through inner membrance, enter
Middle film layer of smooth muscle cells reaches target position and worked.It was found that using transdermal enhancer as pharmaceutical carrier, medicine can be reduced and passed through
The resistance of endothelium, ancillary drug passes rapidly through endothelium, diffusion, reached by substrate in film.Therefore, can be by medicament elution
Sacculus or bracket for eluting medicament etc. carry in the medication coat of medicine apparatus and add transdermal enhancer, medicine is penetrated into endothelium more quickly
And substrate, reach tunicae media vasorum and play the effect for suppressing smooth muscle cell proliferation.
The present invention provides a kind of medicine-coated balloon, including balloon body and the medicine for being covered in the balloon body surface
Coating.The medication coat contains active medicine and carrier.The active medicine includes anti-restenosis drugs or anti-proliferative drug.
The carrier includes transdermal enhancer.When the medicine-coated balloon is placed into human body, after medication coat contact with vascular wall extruding, work
Property medicine is discharged and is transferred to blood vessel inserting target site.Transdermal enhancer carrier function in medication coat is thin in blood vessel endothelium
Born of the same parents, change the structure of endothelial cell, influence the permeability of endothelial cell, accelerate medicine penetrate diseased region endangium and to
Middle film diffusion, so that medicine is absorbed by tissue more quickly, and increases the total dose being absorbed by tissue, be advantageous to medicine
Be retained in tunicae media vasorum layer persistently plays drug effect to thing for a long time.
In one of the embodiments, the quality of the active medicine and the carrier is (0.5~49) than scope：1.
In one of the embodiments, the carrier also includes dispersant.Due to lipophilic anti-restenosis drugs or anti-
Hypertrophic medicine is easily mutually assembled, and the dispersant of Lipophilicity can be combined quickly with lipophilic drugs, interval drug
Particle, so as to reduce the probability reunited between drug molecule, improve coating uniformity.Secondly, after adding dispersant, can improve
The fineness of medication coat particle, reduces the size of drug particles, and the medicine of small size is more easy to be absorbed.In addition, with dispersant knot
Its specific surface area increase of the drug molecule of conjunction, solubility improve, and the adsorption capacity after being contacted with blood vessel lipophilic structure improves, and helps
In transfer of the medication coat from balloon surface to vascular wall.In addition, after dispersant is combined with lipophilic drugs, conveyed in sacculus
Lipophilic drugs are formed in journey and protected, are advantageous to the adhesion of medication coat and balloon body surface, reduce medication coat defeated
Loss during sending, ensure that expanding adherent forecourt capsule, there is sufficient medicine to be reprinted to tissue.Therefore, when dispersant is with promoting thoroughly
Agent acts synergistically, and can not only accelerate the release process of medicine and promote medicine in the osmotic absorption of inner skin surface, while can reduce
The medication coat of balloon surface and then obtains more preferable therapeutic effect in the particles from getting loose and process losses of course of conveying.
In one of the embodiments, the quality of the dispersant and transdermal enhancer ratio scope is (0.01~50): 1.
In one of the embodiments, the anti-proliferative drug is selected from taxol, paclitaxel derivatives, rapamycin or thunder
At least one of pa adm derivative.
In one of the embodiments, the transdermal enhancer is selected from alcohol compound and its derivative, aliphatic acid and its derivative
At least one of thing, aromatic acid and its derivative.Different from the transdermal patch or other medicaments through percutaneous drug delivery of routine
The transdermal enhancer used, because the composition of vascular wall is different from skin, endovascular physiological environment also with the environment of percutaneous dosing not
Together, blood pH, blood flow should be overcome by being suitable as the transdermal enhancer of Vascular implantation class or intervention class medicine equipment medication coat
The influence of the hemodynamic environment of continuous erosion, and can not be with other matter interactions in blood.
In one of the embodiments, the alcohol compound is selected from fatty alcohol or polyalcohol, and the fatty alcohol is selected from pungent
Alcohol, decyl alcohol, laruyl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, arachidic alcohol or docosanol.The polyalcohol be selected from propane diols,
Glycerine or polyethylene glycol.
In one of the embodiments, the aliphatic acid is selected from octanoic acid, capric acid, laurate, myristic acid, palmitic acid, tristearin
Acid, arachidic acid, consistent lubricant acid, oleic acid, linoleic acid, leukotrienes or arachidonic acid.
In one of the embodiments, the aromatic acid is selected from benzoic acid, phenylacetic acid, syringic acid, cinnamic acid, o-hydroxy
Formic acid, P-hydroxybenzoic acid, p-aminobenzoic acid, paraaminomethyl benzoic acid, PAS or phthalic acid.
In one of the embodiments, the derivative includes esters, amide-type, anhydrides or salt；The salt bag
Include magnesium salts, sodium salt, zinc salt, calcium salt, barium salt or mantoquita.
In one of the embodiments, the transdermal enhancer is selected from laruyl alcohol, myristyl alcohol, stearyl alcohol, laurate, palm
Acid, stearic acid, magnesium stearate, odium stearate, zinc stearate, stearmide, isobutyl palmitate, linoleic acid, leukotrienes, single oil
Acid glyceride, polyoxyethylene stearic acid ester, sodium benzoate, cinnamic acid, septichen, P-hydroxybenzoic acid, to amino water
At least one of poplar acid or phthalic anhydride.
In one of the embodiments, the dispersant is selected from acetate, maleate, polyvinylpyrrolidone, amber
Hydrochlorate, ascorbate, citrate, tartrate, lactate, oxalates, aspartate, nicotinate, gluconate,
Cetomacrogol 1000, polyethylene glycol 2000, acetamide, poloxamer, pentaerythrite, glutamate, vanillate, hydroxypropyl first
At least one of base cellulose or Lactobionate.
In one of the embodiments, content range of the active medicine on the balloon body surface is 0.5~20 μ
g/mm2。
In one of the embodiments, the medicine-coated balloon is used to the active medicine being transported to blood vessel or tube chamber
It is interior.The blood vessel includes coronary artery, peripheral arterial blood vessel or cerebral artery vessel.The tube chamber includes esophagus, air flue, intestines
Road, biliary tract, uterine neck, the urinary tract, prostate or brain passage.The peripheral arterial blood vessel includes leg arteries, further, including
Common iliac artery, arteria iliaca externa, femoral artery Huo popliteal arteries.
The present invention compared with prior art, at least with advantages below and beneficial effect：
(1) transdermal enhancer is contained in the medication coat of medicine-coated balloon of the invention, medicine is discharged to blood from balloon surface
It after tube wall, can quickly be absorbed by vascular tissue, overcome high amount of drug before being absorbed by vascular tissue just by swiftly flowing blood
Stream washes away the shortcomings that loss；
(2) medicine is in the presence of transdermal enhancer, film in being reached more quickly through inner membrance, therefore the dose being absorbed by tissue
Higher, enough drug is retained in tunicae media vasorum layer for a long time, can extend the continuous action time of medicine, ensures that medicine can continue
Play greatest treatment efficacy and suppress ISR at a specified future date.
Brief description of the drawings
Fig. 1 is inserted in healthy miniature pig body after expansion for the medicine-coated balloon of the embodiment of the present invention 1 to 7 and comparative example 1,
The tunicae media vasorum drug release patterns of balloon expandable section target vessel；
Fig. 2 is that the medicine-coated balloon that the embodiment of the present invention 1 provides is inserted in healthy miniature pig body after expansion, medicine after 28 days
The pathological section H＆E colored graphs of thing coating sacculus surrounding tissue；
Fig. 3 is that the medicine-coated balloon that the embodiment of the present invention 1 provides is inserted in healthy miniature pig body after expansion, medicine after 28 days
Pathological section α-actin the colored graphs of thing coating sacculus surrounding tissue；
Fig. 4 is that the medicine-coated balloon that the embodiment of the present invention 1 provides is inserted in healthy miniature pig body after expansion, medicine after 28 days
The pathological section Masso trichrome stain figures of thing coating sacculus surrounding tissue；
Fig. 5 is that the medicine-coated balloon that the embodiment of the present invention 1 provides is inserted in healthy miniature pig body after expansion, medicine after 28 days
The pathological section Movat colored graphs of thing coating sacculus surrounding tissue；
Fig. 6 is particles from getting loose micro- photograph of the medicine-coated balloon of the offer of the embodiment of the present invention 1 after in-vitro simulated test
Piece；
Fig. 7 is particles from getting loose micro- photograph of the medicine-coated balloon of the offer of the embodiment of the present invention 2 after in-vitro simulated test
Piece；
Fig. 8 is particles from getting loose micro- photograph of the medicine-coated balloon of the offer of the embodiment of the present invention 3 after in-vitro simulated test
Piece；
Fig. 9 is particles from getting loose micro- photograph of the medicine-coated balloon of the offer of the embodiment of the present invention 4 after in-vitro simulated test
Piece；
Figure 10 is particles from getting loose micro- photograph of the medicine-coated balloon of the offer of the embodiment of the present invention 5 after in-vitro simulated test
Piece；
Figure 11 is particles from getting loose micro- photograph of the medicine-coated balloon of the offer of the embodiment of the present invention 6 after in-vitro simulated test
Piece；
Figure 12 is particles from getting loose micro- photograph of the medicine-coated balloon of the offer of the embodiment of the present invention 7 after in-vitro simulated test
Piece；
Figure 13 is particles from getting loose microphoto of the medicine-coated balloon of comparative example 1 after in-vitro simulated test.
Embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, it is right below in conjunction with drawings and Examples
The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and
It is not used in the restriction present invention.
Unless otherwise defined, the technical field of all technologies used in the present invention and scientific terminology with belonging to the present invention
The implication that is generally understood that of technical staff it is identical.Present invention term used in the description is intended merely to describe specific reality
Apply the purpose of example, it is not intended that in the limitation present invention.
Embodiment 1
Using 11mg taxols as active medicine, 17mg laurate is as transdermal enhancer, 5mg hydroxypropyl methyl cellulose conducts
Dispersant, with 7mL ethanol and 4mL purified water mixed preparing drug solutions.By PTA foley's tubes, (size is：Diameter 4mm, it is long
Sacculus 40mm) in ten thousand grades of clean environments flap be three foldings after, under hundred grades of clean environments, by drug solution precise injection
On the surface of sacculus after device drop coating to flap and dry, repeat drop coating until the drug concentration of balloon surface reaches 3 μ g/mm2,
After drying at room temperature 24 hours, packaging, ethylene oxide sterilizing, the medicine-coated balloon of the present embodiment is obtained.Carrier in the present embodiment
Gross weight is 22mg, and the mass ratio of active medicine and carrier is 0.5, and the mass ratio of dispersant and transdermal enhancer is 0.29 in carrier.
Embodiment 2
Make 495mg taxols as active medicine, 10mg isobutyl palmitates as transdermal enhancer, 0.1mg sodium citrates
For dispersant, with 20mL isopropanol mixed preparing drug solutions.By the sacculus of PTA foley's tubes (diameter 4mm, long 40mm) ten thousand
Level clean environment in flap be three foldings after, under hundred grades of clean environments, by the surface of the sacculus after drug solution drop coating to flap
Go up and dry, repeat drop coating until the drug concentration of the balloon surface reaches 0.5 μ g/mm2, drying at room temperature is after 24 hours, bag
Dress, ethylene oxide sterilizing, obtains the medicine-coated balloon of the present embodiment.Total weight of carrier is 10.1mg in the present embodiment, activity
The mass ratio of medicine and carrier is 49, and the mass ratio of dispersant and transdermal enhancer is 0.01 in carrier.
Embodiment 3
Purified 120mg taxols as active medicine, 36mg sodium benzoates as transdermal enhancer with 10mL ethanol and 4mL
Water mixed preparing drug solution.By the sacculus of PTA foley's tubes (diameter 4mm, long 40mm), flap is in ten thousand grades of clean environments
After three foldings, under hundred grades of clean environments, the balloon surface after drug solution is sprayed into flap with spraying equipment, make balloon surface
Drug concentration reach 2 μ g/mm2, drying at room temperature is after 24 hours, packaging, ethylene oxide sterilizing, and the medicine for obtaining the present embodiment applies
Layer sacculus.The mass ratio of active medicine and carrier is 3.33 in the present embodiment.
Embodiment 4
Using 100mg taxols as active medicine, 50mg magnesium stearates are as transdermal enhancer, 5mg cetomacrogol 1000 conducts
Dispersant, with 10mL ethanol and 4mL purified water mixed preparing drug solutions.By PTA foley's tubes (diameter 4mm, long 40mm)
Sacculus in ten thousand grades of clean environments flap be three foldings after, under hundred grades of clean environments, drug solution is sprayed to spraying equipment
In balloon surface after flap, balloon surface drug concentration is set to reach 3 μ g/mm2, drying at room temperature is after 24 hours, packaging, epoxy second
Alkane sterilizes, and obtains the medicine-coated balloon of the present embodiment.Total weight of carrier is 55mg in the present embodiment, active medicine and carrier
Mass ratio is 1.82, and the mass ratio of dispersant and transdermal enhancer is 0.1 in carrier.
Embodiment 5
Using 120mg taxols as active medicine, 3mg laruyl alcohols as transdermal enhancer, 9mg acetamides as dispersant, with
2mL ethanol and 0.4mL purified water mixed preparing drug solutions.By the sacculus of PTA foley's tubes (diameter 4mm, long 40mm) ten thousand
Level clean environment in flap be three foldings after, under hundred grades of clean environments, after drug solution is sprayed into flap with spraying equipment
In balloon surface, the drug concentration of balloon surface is set to reach 2.5 μ g/mm2, after 24 hours, packaging, oxirane goes out drying at room temperature
Bacterium, obtain the medicine-coated balloon of the present embodiment.Total weight of carrier is 12mg, active medicine and carrier quality in the present embodiment
Than for 10, the mass ratio of dispersant and transdermal enhancer is 3 in carrier.
Embodiment 6
Using 12mg taxols as active medicine, as transdermal enhancer, 5mg polyvinylpyrrolidones are used as to be divided 1mg stearyl alcohols
Powder, with 100mL isopropanols and 20mL purified water mixed preparing drug solutions.By PTCA foley's tubes (diameter 3mm, long 20mm)
Sacculus in ten thousand grades of clean environments flap be three foldings after, under hundred grades of clean environments, drug solution is sprayed with spraying equipment
In balloon surface after to flap, balloon surface drug concentration is set to reach 1.5 μ g/mm2, drying at room temperature is after 24 hours, packaging, ring
Oxidative ethane sterilizes, and obtains the medicine-coated balloon of the present embodiment.Total weight of carrier is 6mg, active medicine and load in the present embodiment
The mass ratio of body is 2, and the mass ratio of dispersant and transdermal enhancer is 5 in carrier.
Embodiment 7
Using 20mg taxols as active medicine, 0.5mg stearmides are as transdermal enhancer, 25mg polyethylene glycol 2000 conducts
Dispersant, with 10mL ethanol and 5mL purified water mixed preparing drug solutions.By PTA foley's tubes (diameter 4mm, long 40mm)
Sacculus in ten thousand grades of clean environments flap be three foldings after, under hundred grades of clean environments, drug solution is sprayed to spraying equipment
In balloon surface after flap, the drug concentration of balloon surface is set to reach 5 μ g/mm2, drying at room temperature is after 24 hours, packaging, epoxy
Ethane sterilizes, and obtains the medicine-coated balloon of the present embodiment.Total weight of carrier is 25.5mg, active medicine and load in the present embodiment
The mass ratio of body is 0.78, and the mass ratio of dispersant and transdermal enhancer is 50 in carrier.
Embodiment 8
Make 120mg rapamycins as active medicine, 4mg glyceryl monooleates as transdermal enhancer, 24mg poloxamers
For dispersant, with 2mL ethanol and 10mL purified water mixed preparing drug solutions.By PTA foley's tubes (diameter 5mm, long 80mm)
Sacculus in ten thousand grades of clean environments flap be five foldings after, under hundred grades of clean environments, drug solution is sprayed with spraying equipment
In balloon surface after to flap, the drug concentration of balloon surface is set to reach 10 μ g/mm2, drying at room temperature is after 24 hours, packaging,
Ethylene oxide sterilizing, obtain the medicine-coated balloon of the present embodiment.Total weight of carrier is 28mg in the present embodiment, active medicine and
The mass ratio of carrier is 4.29, and the mass ratio of dispersant and transdermal enhancer is 6 in carrier.
Embodiment 9
Using 210mg rapamycins as active medicine, 2mg stearic acids polyoxyethylene ester is as transdermal enhancer, 40mg seasons penta 4
Alcohol is as dispersant, with 45mL ethanol and 5mL purified water mixed preparing drug solutions.By PTA foley's tubes (diameter 7mm, length
Sacculus 120mm) in ten thousand grades of clean environments flap be five foldings after, under hundred grades of clean environments, drug solution is set with spraying
For in the balloon surface sprayed to after flap, the drug concentration of balloon surface is set to reach 20 μ g/mm2, drying at room temperature is after 24 hours,
Packaging, ethylene oxide sterilizing, obtains the medicine-coated balloon of the present embodiment.Total weight of carrier is 42mg in the present embodiment, activity
The mass ratio of medicine and carrier is 5, and the mass ratio of dispersant and transdermal enhancer is 20 in carrier.
Embodiment 10
Using 10mg rapamycins as active medicine, 2mg magnesium stearates are as transdermal enhancer, with 20mL ethanol mixed preparing medicines
Thing solution.By the sacculus of PTCA foley's tubes (diameter 2.5mm, long 18mm) in ten thousand grades of clean environments flap be three foldings after,
Under hundred grades of clean environments, in the balloon surface after drug solution is sprayed into flap with spraying equipment, make the medicine of balloon surface
Concentration reaches 3.5 μ g/mm2, drying at room temperature is after 24 hours, packaging, ethylene oxide sterilizing, obtains the medication coat ball of the present embodiment
Capsule.Total weight of carrier is 2mg in the present embodiment, and the mass ratio of active medicine and carrier is 5.
Comparative example 1
50mg taxols is molten with 5mL ethanol mixed preparing medicines as carrier as active medicine, 20mg Iopromides
Liquid.By the sacculus of PTA foley's tubes (diameter 4mm, long 40mm) in ten thousand grades of clean environments flap be three foldings after, in hundred grades of cleanings
Under environment, in the balloon surface after drug solution is sprayed into flap with spraying equipment, the drug concentration for making balloon surface is 3 μ
g/mm2, drying at room temperature 24 hours, packaging, ethylene oxide sterilizing, obtain the medicine-coated balloon of comparative example 1.It is purple in comparative example 1
The mass ratio of China fir alcohol active medicine and carrier is 2.5.
Drug release test
The medicine-coated balloon that embodiment 1 to 7 and comparative example 1 provide is respectively implanted in healthy miniature pig body, in outside ilium
Pressurising expansion is carried out at arteries, withdraws from medicine-coated balloon, completes balloon expandable operation, and respectively in 30min, 24h, 7
Follow-up when it and 28 days.During follow-up, the target vessel when balloon expandable that first dissociates is performed the operation around medicine-coated balloon, with containing heparin
0.1mol/L PBS solutions (per 1000mlPBS units containing heparin 25000) slow rinse target vessel 3 times, by the three of target vessel
Rotating fields strip off separation, then inner membrance, middle film and outer membrane are respectively obtained after collecting.Using liquid chromatograph-mass spectrometer (referred to as：
LC-MS/MS the medicament contg in the middle membrane tissue of balloon expandable section target vessel) is measured.LC-MS/MS test condition is：
Liquid chromatogram instrument：The type liquid chromatographic systems of Agilent 1200 (Agilent company), the quaternary of type containing G1312A is defeated
Liquid pump, G1322A type vacuum degassing machines；
Mass spectrometer：API4000 QTRAP type triple quadrupole bars tandem mass spectrometers (AB Sciex companies), it is equipped with electron spray
Ionization source is (referred to as：ESI)；
Analytical column：Venusil XBP C8 chromatographic columns (Beaune Ai Jieer scientific ＆ technical corporation), size：2.1 × 50mm, 5 μm；
Mobile phase condition：A phases (containing 0.1% aqueous formic acid), B phases (containing 0.1% formic acid acetonitrile solution), gradient is washed
It is de-；
Column temperature：30℃；
Mass Spectrometry Conditions：ESI positive ion detection patterns.
The medicament contg of film is as vertical in the target vessel measured using four follow up time points as abscissa, each time point
Coordinate, the drug release patterns of film in the target vessel of embodiment 1 to 7 and comparative example 1 is drawn respectively, as shown in Figure 1.The curve is anti-
Retention behavior of the medicine by target vessel tissue resorption and medicine in target vessel in membrane tissue is reflected.
Referring to Fig. 1, as a result show：Compared with comparative example 1, during 30min, the medicine of the medicine-coated balloon of embodiment 1 to 7
Thing coating, possesses the higher ability by target vessel tissue resorption.During 24h, the medicine of membrane tissue in the target vessel of embodiment 1 to 7
Thing content increases sharply, and the medicine-coated balloon of comparative example 1, and medicament contg does not increase during 24h, illustrates the embodiment of the present invention
The medication coat of 1 to 7 medicinal balloon rapidly penetrates into film in target vessel in the presence of transdermal enhancer.And comparative example 1
The biological barrier of the more difficult transmission target endangium of medication coat, it passes through instantaneous expanding extruding in initial time, can only rely on solid
Some a small amount of medicines of concentration official post pass through inner membrance；And in the time afterwards, medicine does not enter back into film in target vessel, comes into
A small amount of medicine of film gradually uses up in target vessel, causes the medicament contg of film in target vessel that the rule of monotone decreasing is presented.This enters
One step demonstrates the remarkable effect that transdermal enhancer is added in the present invention.In the long-time follow-up of 7 days and 28 days, embodiment 1 to 7
The medicament contg of film is not further added by target vessel, is illustrated between 24h and 7 day, medicine film osmotic absorption and target into target vessel
Metabolism of the tunicae media vasorum to medicine is using balance is reached, and after 7 days, total dose of film gradually reduces in target vessel.And comparative example 1
In follow-up in 7 days, the dose of film was seldom in target vessel, and dose during follow-up in 28 days is substantially zeroed.
As seen from Figure 1, instantaneous medicine reprinting amount size, over time, embodiment 1 to 7 no matter are expanded
Medicine can quickly absorb and into target vessel wall, and start gradually to increase in 24h, and maintain longer time.This
The excellent medicine reserve capability of kind so that even relatively low initial reprinting, also possess higher drug concentration in long term.Explanation
The medicine-coated balloon of embodiment 1 to 7, active component can be locally discharged to focus in the given time, give full play to medicine
The therapeutic action of thing, extend drug treating time, improve the bioavailability of medicine.
Also, because within the same expansion time, the medicine-coated balloon that the embodiment of the present invention 1 to 7 provides is by blood vessel
The dose of tissue resorption is more than the dose that is absorbed by vascular tissue of medicine-coated balloon of the offer of comparative example 1, decrease by
Blood flow washes away the dose of loss, and when needing to reach same mass effect, medicine-coated balloon provided by the invention can reduce
Active agent delivery dosage in medication coat, harm of the medicine to diseased region and other organs is alleviated, controls medicine
Toxic side effect.
Histopathological study
The medicine-coated balloon that embodiment 1 to 6 and comparative example 1 provide is respectively implanted in healthy miniature pig body, in outside ilium
Pressurising is expanded at arteries, withdraws from medicine-coated balloon, completes balloon expandable operation, and follow-up in 28 days after surgery respectively.With
During visit, the target vessel when balloon expandable that first dissociates is performed the operation around medicine-coated balloon is molten with the 0.1mol/L PBS containing heparin
Liquid (per 1000mlPBS units containing heparin 25000) slow rinse target vessel 3 times.By the fine rule knot of the branch vessel at target vessel
Prick, 1cm is respectively retained at the closely remote both ends of target vessel, ligature fixation again after irrigating formalin, make multiple paraffin-embedded tissues and cut
Piece is used for histopathological analysis.
By taking embodiment 1 as an example, describe histopathological analysis method in detail, specifically comprise the following steps：First to embodiment 1
The multiple histotomies of target vessel carry out respectively H＆E dyeing, α-actin dyeing, Masso trichrome stains and Movat dyeing, respectively
Obtain Fig. 2 to Fig. 5 colored graph.Inflammatory cell in Fig. 2 to Fig. 5 colored graph, the indigo plant in Masso trichrome stains respectively
Color area and wall thickness, which are lost, is given a mark, to investigate inflammatory reaction, collagen fibrous proteins deposition and middle film smooth muscle loss situation.
It is that producing suppression to smooth muscle cell proliferation makees when the medicine of medicine-coated balloon acts on tissue to investigate principle
With, while start inflammatory reparation reaction, produce collagen fibrous proteins deposition losing smooth muscle cell position.
Three investigation respective scoring criterions of index are as follows：
A, inflammatory reaction scoring criterion
Inflammation integral and calculating bibliography standard is divided into 4 grades.Repeatedly observation calculates average value.
0 point：There is no inflammatory cell (lymphocyte, eosinophil, macrophage etc.) around middle film and inner membrance.
1 point：There is a small amount of inflammatory cell infiltration around middle film and inner membrance.
2 points：There is the inflammatory cell infiltration of moderate in inner membrance, middle film and outer membrane, account for 25~50% vessel areas.
3 points：There is substantial amounts of inflammatory cell in inner membrance, middle film and outer membrane, around whole blood vessel, occupy more than 50% blood vessel face
Product.
B, collagen fibrous proteins deposition scoring criterion
0 point：There is no any loss.
1 point：Blue colored area in trichrome stain<25%.
2 points：Blue colored area in trichrome stain is 25~50%.
3 points：Blue colored area in trichrome stain is 51~75%.
4 points：Blue colored area in trichrome stain is>75%.
C, middle film smooth muscle loses scoring criterion
0 point：There is no any loss.
1 point：<25% wall thickness is lost.
2 points：25~50% wall thickness is lost.
3 points：51~75% wall thickness is lost.
4 points：>75% wall thickness is lost.
Identical histopathological analysis is carried out to the histotomy of embodiment 2 to 6 and comparative example 1, it is no longer superfluous herein
State.
The medicine-coated balloon histopathological analysis result of embodiment 1 to 6 and comparative example 1 see the table below 1.
The histopathology integral result of 28 days after the treatment of the medicine-coated balloon of table 1
As a result show：The medicine-coated balloon of embodiment 1 to 6 is compared with the medicine-coated balloon of comparative example 1, and it is to periphery
There were significant differences for the influence of vascular tissue.
First, the inflammatory integration of embodiment 1 to 6 is higher, and inner membrance, middle film and outer membrane have the inflammatory cell infiltration of moderate,
Illustrate surrounding target vessel tissue to the medicine aitiogenic time in the medication coat of embodiment 1 to 6 faster, i.e., medicine act on
To vascular tissue time faster.Secondly, the middle film smooth muscle of embodiment 1 to 6 is lost and fibrin deposition is higher, illustrates medicine
Thing produces the startup time of inhibitory action faster to smooth muscle cell.
Above-mentioned difference further proves, due to saturating containing promoting in the coating of the medicine-coated balloon of the offer of embodiment 1 to 6
Agent, it can promote film in drug absorption intravasation, accelerate the action time of medicine, reduce the medicine that loss is washed away by blood flow
Amount, ensure that the medicament contg at a specified future date in vascular tissue.
In-vitro simulated particles from getting loose test
By in-vitro simulated test, the medicine-coated balloon of embodiment 1 to 7 and the offer of comparative example 1 is detected in course of conveying
In particles from getting loose situation.Method of testing is as follows：Be 37 DEG C using temperature, flow as 250mL/min purifying Fluid Dynamics blood flow, fit
The silicone tube simulated blood vessel of suitable dimensions, simulates surgical procedure.The medication coat of embodiment 1 to 7 and comparative example 1 is conveyed respectively
For sacculus to target site, dilating sacculus makes its extrusion simulation blood vessel, and the medication coat of balloon surface is eluted, particles from getting loose and with mould
Intend blood flow to be washed to simulated blood vessel distal end.
The particle size and quantity of simulated blood vessel distal end are detected by particulate instrument, as a result as shown in table 2.And by aobvious
Micro- photo, measure the specific size and pattern of 100 μm of ＞ large scale particulate.The particles from getting loose microphoto point of embodiment 1 to 7
Not as shown in Fig. 6 to 12, the particles from getting loose microphoto of comparative example 1 is as shown in figure 13.
The in-vitro simulated particles from getting loose test result of table 2
As shown in Table 2：Compared with comparative example 1, the medicine-coated balloon of embodiment 1 to 7 simulated blood vessel by conveying and
After process of expansion, the particle number that each size range comes off is less, and the maximum particle diameter of shed particles is smaller, i.e. particles from getting loose
Level is better than comparative example 1.
Thus illustrate, the dispersant added in the medication coat of embodiment 1 to 7 has good dispersibility, can drop
The particle size and quantity to be come off during low medicine-coated balloon use.Principle is that dispersant has interval action, Ke Yiti
The fineness of high medication coat particle, makes coating be evenly distributed.Prevent medicine before medicinal balloon is presented to target site too early
Release.
In-vitro simulated course of conveying loss test
With the target vessel of isolated pig coronary blood pipe die personification body coronary artery system, carried out in vitro in simulated blood vessel model
In-vitro simulated course of conveying loss test.Investigate the medicine during medicine-coated balloon is delivered to target site through delivery sheath
Amount loss.
The medicine-coated balloon for respectively preparing embodiment 1 to 7 and comparative example 1 is inserted in in-vitro simulated vascular pattern.
Floated 90 seconds in in-vitro simulated blood vessel model, then take out medicine-coated balloon, be utilized respectively high performance liquid chromatography (referred to as：
HPLC medicine remaining on medicine-coated balloon) is analyzed, and course of conveying drug loss rate is calculated as follows：
Course of conveying drug loss rate=(medicament contg-remnants of balloon surface initial load medicament contgs)/sacculus
Medicament contg × 100% of surface initial load.
HPLC test conditions are：
Instrument：Japanese Shimadzu LC-20A type high performance liquid chromatographs；
Chromatographic column：Agilent ZORBAX SB-C18 chromatographic columns, size：4.6 × 250mm, 5 μm；
Mobile phase：Methanol:Acetonitrile:Water=230:360:410；
Column temperature：30℃；
Detector：UV-vis detector, Detection wavelength 227nm；
Flow velocity：1.0mL/min.
HPLC measurement results are as shown in table 3：
3 in-vitro simulated course of conveying of table loses test result
The result of table 3 shows：Compared with comparative example 1, the medicine-coated balloon that the embodiment of the present invention 1 to 7 provides is being delivered to
During target site, loss of the medicine in simulated blood vessel system is reduced.Illustrate the rush added in the medication coat of the present invention
Saturating agent not only without the adhesion for influenceing medication coat and sacculus, is also used as affinity agent, and enhancing balloon surface applies with medicine
Adhesion between layer.Simultaneously as dispersant reduces the fineness of medication coat particle, therefore the two acts synergistically, and enters one
Step adds the adhesion between balloon surface and medication coat, improves in course of conveying, medication coat resists crooked route
And the ability of the influence of frictional force.
To sum up, medicine-coated balloon provided by the invention, medication coat include transdermal enhancer.When medicine-coated balloon is set to
Enter human body, after balloon expandable is adherent, active medicine is discharged and is transferred to blood vessel inserting target site.Now, medication coat
In transdermal enhancer carrier function in vascular endothelial cell, change the structure of endothelial cell, influence the permeability of endothelial cell, accelerate
Medicine penetrates the endangium of diseased region and to middle film diffusion, so that medicine is absorbed by tissue more quickly, and
Increase the total dose being absorbed by tissue, being advantageous to medicine, being retained in tunicae media vasorum layer persistently plays drug effect for a long time.Also, needing
When reaching same mass effect, medicine-coated balloon provided by the invention can reduce the active agent delivery in medication coat
Dosage, harm of the medicine to diseased region and other organs is alleviated, controls poisonous side effect of medicine.
The present invention can not only promote active drug by selecting the species of appropriate transdermal enhancer and its ratio with active medicine
Thing film from endangium rapid osmotic intravasation, while other performances of medication coat are not influenceed, reduce conveying and expansion
The particles from getting loose of process and process losses rate etc..In medicine-coated balloon provided by the invention, the quality of active medicine and carrier
It is (0.5~49) than scope：1.When the mass ratio of active medicine and carrier is too big, substantial amounts of active medicine can not be with balloon body
Surface strong bonded, the fastness of medication coat reduce, and course of conveying loss is larger；And carrier can not play and promote medicine to inhale
The effect of receipts, the dose absorbed by vascular tissue is relatively low, influences to suppress the effect of ISR at a specified future date.When active medicine and carrier
Mass ratio is too small, and active medicine content is too low, can influence the validity of medication coat again.
Medicine-coated balloon provided by the invention, dispersant can also be included in the carrier of medication coat, due in carrier
Transdermal enhancer and dispersant produce synergy, on the premise of the reprinting rate of medication coat is ensured, medicine can not only be promoted to exist
The osmotic absorption of inner skin surface, the dose of film in intravasation is improved, while the medication coat that can reduce balloon surface is conveying
The particles from getting loose and process losses of process, and then obtain more preferable therapeutic effect.
Medicine-coated balloon provided by the invention, the quality of dispersant and transdermal enhancer ratio scope is (0.01~50) in carrier
∶1.This scope can take into account the dispersive property of medication coat simultaneously and promote absorbent properties.When dispersant dosage is excessive, in order to not influence
The mass ratio of active medicine and carrier, transdermal enhancer dosage can be reduced accordingly in carrier, be unable to reach and promoted active medicine to blood vessel
The effect of middle film osmotic absorption.When dispersant dosage is too small, active medicine may reunite, and form more bulky grain, lead
Cause thrombus；And in order to not influence the mass ratio of active medicine and carrier, transdermal enhancer dosage can accordingly increase, and cause medication coat
Firmness reduces, and increase course of conveying loss, reduces the rate of medicine reprinting at once.
Medicine-coated balloon provided by the invention can be used for active medicine conveying blood vessel into the human body or tube chamber
Target site, treat blood vessel or it is intraluminal it is narrow, prevent inner membrance or epithelial proliferation.The blood vessel includes coronary artery, outer
All arteries or cerebral artery vessel.The tube chamber includes esophagus, air flue, enteron aisle, biliary tract, uterine neck, the urinary tract or prostate.Institute
Stating peripheral arterial blood vessel includes leg arteries, further, including common iliac artery, arteria iliaca externa, femoral artery Huo popliteal arteries.
It should be noted that although in embodiment 1 to 10, only with PTA sacculus or PTCA sacculus to the specific of the present invention
Embodiment schematically illustrates, technical scheme provided by the invention can be used for other insertion types carry medicine medicine equipments or
Implanted carries medicine medicine equipment.Such as support, plugging device, orthopaedics implant, gear division implant, suture or bolt.The branch
Frame includes intravascular stent, trachea bracket, esophageal stents, urethra rack, intestinal stent or biliary tract rack.The orthopaedics implant bag
Include fixing screws, fixing rivet or hone lamella.As long as adding transdermal enhancer into medication coat, it and the insertion type are carried into medicine medical treatment
Apparatus or implanted carry the contact of medicine medical apparatus surface or are filled in inside it, you can promote medicine to be absorbed by tissue, drop
It is low that the dose of loss is washed away by blood flow, improved by the dose of tissue absorption, improve insertion type and carry medicine medicine equipment or implantation
Formula carries the clinical therapeutic efficacy of medicine medicine equipment.
Embodiments of the present invention are described above in association with accompanying drawing, but the invention is not limited in above-mentioned tool
Body embodiment, above-mentioned embodiment is only schematical, rather than restricted, the ordinary skill people of this area
Member in the case of present inventive concept and scope of the claimed protection is not departed from, can also make very under the enlightenment of the present invention
Multi-form, these are belonged within the protection of the present invention.
Claims (14)
1. a kind of medicine-coated balloon, including balloon body and the medication coat for being covered in the balloon body surface, the medicine
Thing coating contains active medicine and carrier, and the active medicine includes anti-proliferative drug, it is characterised in that the carrier includes promoting
Saturating agent.
2. medicine-coated balloon according to claim 1, it is characterised in that the quality of the active medicine and the carrier
It is (0.5~49) than scope：1.
3. medicine-coated balloon according to claim 1, it is characterised in that the carrier also includes dispersant.
4. medicine-coated balloon according to claim 3, it is characterised in that the quality of the dispersant and the transdermal enhancer
It is (0.01~50) than scope: 1.
5. medicine-coated balloon according to claim 1, it is characterised in that the anti-proliferative drug is selected from taxol, thunder
At least one of pa mycin, paclitaxel derivatives or rapamycin derivative.
6. medicine-coated balloon according to claim 1, it is characterised in that the transdermal enhancer be selected from alcohol compound and its
At least one of derivative, aliphatic acid and its derivative, aromatic acid and its derivative.
7. medicine-coated balloon according to claim 6, it is characterised in that the alcohol compound is selected from fatty alcohol or more
First alcohol, the fatty alcohol are selected from octanol, decyl alcohol, laruyl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, arachidic alcohol or docosanol,
The polyalcohol is selected from propane diols, glycerine or polyethylene glycol.
8. medicine-coated balloon according to claim 6, it is characterised in that the aliphatic acid is selected from octanoic acid, capric acid, bay
Acid, myristic acid, palmitic acid, stearic acid, arachidic acid, consistent lubricant acid, oleic acid, linoleic acid, leukotrienes or arachidonic acid.
9. medicine-coated balloon according to claim 6, it is characterised in that the aromatic acid be selected from benzoic acid, phenylacetic acid,
Syringic acid, cinnamic acid, septichen, P-hydroxybenzoic acid, p-aminobenzoic acid, paraaminomethyl benzoic acid, to amino water
Poplar acid or phthalic acid.
10. medicine-coated balloon according to claim 6, it is characterised in that the derivative include esters, amide-type,
Anhydrides or salt；The salt includes magnesium salts, sodium salt, zinc salt, calcium salt, barium salt or mantoquita.
11. medicine-coated balloon according to claim 1, it is characterised in that the transdermal enhancer is selected from laruyl alcohol, nutmeg
Alcohol, stearyl alcohol, laurate, palmitic acid, stearic acid, magnesium stearate, odium stearate, zinc stearate, stearmide, palmitic acid are different pungent
Ester, linoleic acid, leukotrienes, glyceryl monooleate, polyoxyethylene stearic acid ester, sodium benzoate, cinnamic acid, septichen,
At least one of P-hydroxybenzoic acid, PAS or phthalic anhydride.
12. medicine-coated balloon according to claim 3, it is characterised in that the dispersant is selected from acetate, maleic acid
Salt, polyvinylpyrrolidone, succinate, ascorbate, citrate, tartrate, lactate, oxalates, asparagus fern ammonia
Hydrochlorate, nicotinate, gluconate, cetomacrogol 1000, polyethylene glycol 2000, acetamide, poloxamer, pentaerythrite, paddy
At least one of propylhomoserin salt, vanillate, hydroxypropyl methyl cellulose or Lactobionate.
13. medicine-coated balloon according to claim 1, it is characterised in that the active medicine is in the balloon body
The content range on surface is 0.5~20 μ g/mm2。
14. the active medicine is being transported to blood vessel or tube chamber by the medicine-coated balloon described in any one of claim 1 to 13
Application in interior, the blood vessel include coronary artery, peripheral arterial blood vessel or cerebral artery vessel；The tube chamber includes food
Road, air flue, enteron aisle, biliary tract, uterine neck, the urinary tract or prostate；The peripheral arterial blood vessel includes leg arteries, further,
Including common iliac artery, arteria iliaca externa, femoral artery Huo popliteal arteries.
Priority Applications (2)
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| CN201610865184.7A CN107865982B (en) | 2016-09-28 | 2016-09-28 | Drug-coated balloon |
| PCT/CN2017/099022 WO2018059167A1 (en) | 2016-09-28 | 2017-08-25 | Drug-coated balloon |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610865184.7A CN107865982B (en) | 2016-09-28 | 2016-09-28 | Drug-coated balloon |
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Cited By (4)
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| CN110384854A (en) * | 2019-08-02 | 2019-10-29 | 上海心玮医疗科技有限公司 | A kind of medicinal balloon and preparation method thereof that drug metabolism is controllable |
| CN113018649A (en) * | 2021-02-05 | 2021-06-25 | 北京先瑞达医疗科技有限公司 | Drug delivery catheter with novel structure and preparation method thereof |
| CN113856005A (en) * | 2021-09-26 | 2021-12-31 | 复旦大学附属中山医院 | Drug-coated balloon catheter assembly for promoting tissue repair and fiber connection and use method thereof |
| CN117258050A (en) * | 2023-11-22 | 2023-12-22 | 杭州亿科医疗科技有限公司 | Medicine balloon and preparation method thereof |
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| US20080276935A1 (en) * | 2006-11-20 | 2008-11-13 | Lixiao Wang | Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs |
| CN102883753A (en) * | 2010-03-25 | 2013-01-16 | 路通医疗股份有限公司 | Drug releasing coatings for medical devices |
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| CN105228663A (en) * | 2013-03-15 | 2016-01-06 | 雅培心血管系统有限公司 | Electrophoresis sacculus and conduction sacculus coating |
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| US20080276935A1 (en) * | 2006-11-20 | 2008-11-13 | Lixiao Wang | Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs |
| CN102883753A (en) * | 2010-03-25 | 2013-01-16 | 路通医疗股份有限公司 | Drug releasing coatings for medical devices |
| CN103736154A (en) * | 2013-12-26 | 2014-04-23 | 先健科技(深圳)有限公司 | Medicinal coating balloon catheter |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110384854A (en) * | 2019-08-02 | 2019-10-29 | 上海心玮医疗科技有限公司 | A kind of medicinal balloon and preparation method thereof that drug metabolism is controllable |
| CN113018649A (en) * | 2021-02-05 | 2021-06-25 | 北京先瑞达医疗科技有限公司 | Drug delivery catheter with novel structure and preparation method thereof |
| CN113018649B (en) * | 2021-02-05 | 2022-07-15 | 北京先瑞达医疗科技有限公司 | Drug delivery catheter and preparation method thereof |
| CN113856005A (en) * | 2021-09-26 | 2021-12-31 | 复旦大学附属中山医院 | Drug-coated balloon catheter assembly for promoting tissue repair and fiber connection and use method thereof |
| CN117258050A (en) * | 2023-11-22 | 2023-12-22 | 杭州亿科医疗科技有限公司 | Medicine balloon and preparation method thereof |
| CN117258050B (en) * | 2023-11-22 | 2024-02-23 | 杭州亿科医疗科技有限公司 | Medicine balloon and preparation method thereof |
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| CN107865982B (en) | 2020-09-25 |
| WO2018059167A1 (en) | 2018-04-05 |
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